Mention the word ‘surveillance’, and the people around you are likely to feel uneasy. But methods to monitor and predict the development of cancer are essential to provide the correct treatment at the right time. Now researchers from the Translational Genomics Research Institute in Arizona show that assessing changes to DNA methylation directly in blood may enable physicians to predict a cancer’s next move.
There are still no effective methods to determine which patients harbor residual disease after breast cancer therapy. This means that some patients receive unnecessary chemotherapy, whereas others sometimes receive treatment when it’s too late.
Markers are thus needed to stratify breast cancer patients into groups at high or low risk of developing distant metastasis. Current methods to detect residual disease rely on gene expression analysis. But this requires tumor tissue and only gives information about one particular point in time.
To step up surveillance of breast cancer cells, Legendre et al. decided not to go to the source, but to try and intercept the messenger. Dying tumor cells release cell-free circulating tumor DNA (cfDNA) into the bloodstream, which may provide important clues about cancer progression.
Using whole genome bisulfite sequencing, the team analyzed DNA methylation in cfDNA from 40 metastatic breast cancer patients, 40 healthy individuals and 40 disease-free survivors. Comparisons between methylomes revealed that:
- cfDNA from metastatic breast cancer patients was globally hypomethylated compared to cfDNA from either healthy individuals or disease-free survivors, but it showed focal points of hypermethylation.
- Most hypermethylation occurred in CpG islands near the beginning of genes.
- Analysis of these CpG islands identified a 21 gene hypermethylation signature, including RUNX3, PENK, PAX5 and PCDH10, which are known to be hypermethylated in breast cancer.
Although further studies are required to validate this signature, tests based on it may allow physicians to stay one step ahead of the cancer.
For the full report check out Clinical Epigenetics, September 2015.